Effects of Fuke Qianjin Formula on hormones and their receptors and metabonomics study in uterine fibroids model rats

Objective To investigate the effects of different fractions from Fuke Qianjin Formula(妇科千金方,FKQJF)on uterine leiomyoma(UL)to determine the best fraction.Methods FKQJF was extracted and isolated to obtain polysaccharides(FKP),flavonoids(FKF),and grease(FKG).140 female SPF SD rats were divided into 14 groups[model(MOD),normal control(NC),Gouliuqing(GLQ),Mifepristone(MFST),FKQJF,low,medium,and high dose of polysaccharides(l-FKP,m-FKP,and h-FKP),low,medium,and high dose of flavonoids(l-FKF,m-FKF,and h-FKF),low,medium,and high dose of grease(l-FKG,m-FKG,and h-FKG)],and uterine fibroids model rats were treated with drugs for four weeks.Serum levels of estrogen and progesterone were measured using enzyme-linked immunoassay assay(ELISA)kits.The expression of estrogen receptor(ER-α,ER-β)and progesterone receptor(PR)in the uterus was observed using immunohistochemistry(IHC).Serum metabolite profiles and FKG were analyzed using gas chromatography-mass spectrometry(GC-MS).Results FKQJF,h-FKF,m-FKG,and h-FKG significantly downregulated the estrogen level in the uterine fibroid model rats(P<0.01).FKQJF,h-FKF,and h-FKG significantly reduced the level of progesterone in the uterine fibroid model rats(P<0.01).The levels of ER-α,ER-β,and PR in uterine fibroid model rats were significantly decreased by FKQJF and h-FKG(P<0.01).The levels of ER-α,ER-β,and PR in the fibroid model rats were decreased by m-FKG(P<0.05).Additionally,serum metabolism results revealed that h-FKG and FKQJF could regulate related endogenous metabolites and make the pathological indices of uterine fibroids in rats close to the normal group.Forty-six components were identified in the oil,accounting for 91.97%of the total oil components.Conclusion FKQJF and h-FKG showed a significant anti-myoma activity and significantly improved the pathological state of the uterus in rats with hysteromyoma.The mechanism of action may be related to the regulation of estrogen progesterone and its receptor in uterine fibroid model animals.These findings proved the effect of FKQJF on uterine leiomyoma and provided an experimental basis for its clinical research and application.

妇科千金方及其拆方对盆腔炎性疾病后遗症大鼠的作用

目的研究妇科千金方及其拆方对盆腔炎性疾病后遗症大鼠的作用。方法SD大鼠随机分为正常组、假手术组、模型组、康妇炎组(0.756 g/kg)、妇科千金方组(2.7 g/kg)、抑菌方组(2.7 g/kg)、抗炎方组(2.7 g/kg)、补益方组(2.7 g/kg),灌胃给予相应药物28 d后处死,计算子宫、脾脏、胸腺、肝脏指数,肉眼观察大鼠、输卵管形态学改变,HE染色观察大鼠子宫、输卵管组织病理学变化,ELISA法检测大鼠血清IL-1β、IL-18、IL-6水平,Western blot法检测大鼠子宫组织TGF-β1、CTGF、NLRP3、caspase-1、IL-18蛋白表达,流式细胞术检测大鼠脾脏组织CD4、CD8表达。结果与模型组比较,妇科千金方组、抑菌方组、抗炎方组、补益方组大鼠子宫、脾脏、胸腺指数均降低(P<0.01);妇科千金方组、抗炎方组大鼠子宫肿胀减轻,子宫内膜腺体增多,炎性渗出减轻(P<0.01),血清IL-1β、IL-18、IL-6水平降低(P<0.01);妇科千金方组、抗炎方组、补益组大鼠子宫组织TGF-β1、CTGF蛋白表达降低(P<0.05);妇科千金方组、抗炎方组大鼠子宫组织NLRP3、caspase-1、IL-18蛋白表达降低(P<0.01);妇科千金方组、补益组CD4^(+)/CD8^(+)比值升高(P<0.01)。结论妇科千金方及其拆方对盆腔炎性疾病后遗症大鼠具有保护作用,其抗炎作用机制可能是通过抑制NLRP3小体的活化,从而阻碍caspase-1的活化,降低促炎症因子IL-18的分泌及释放,抑制细胞焦亡而发挥抗炎作用。

妇科千金方质量标志物研究

妇科千金方是治疗妇科炎症性疾病的中药复方,已被认定为国家中药保护品种和国家基本药物目录品种,并已载入《中华人民共和国药典》2020年版,分为妇科千金片和妇科千金胶囊2个品种。妇科千金方由千斤拔、金樱根、穿心莲、功劳木、单面针、鸡血藤、党参和当归8味中药组成。通过梳理妇科千金方的化学成分、质量控制、药动学和药理作用等相关文献并结合实际研究,基于“中药质量标志物理论”进行预测分析,小檗碱、巴马汀、药根碱、新穿心莲内酯苷、穿心莲内酯、新穿心莲内酯苷元、7-O-甲基汉黄芩素、染料木苷、芒柄花苷、染料木素、柚皮素、反式阿魏酸、水杨酸和Z-藁本内酯等专属性高、可测性强,可作为妇科千金方的潜在质量标志物,为其质量控制研究提供参考。